A high-salt diet raises the sodium concentration in the cerebrospinal fluid (CSF [Na+]) in salt-sensitive individuals, an effect that can be mimicked by intracerebroventricular (icv) infusion of NaCl. Increasing CSF [Na+] increases the concentration of an endogenous brain ouabain-like substance(s) (OLS) that inhibits brain Na, K-ATPases, which in turn activates the brain renin-angiotensin system, augmenting sympathetic nervous system activity and blood pressure. It is unknown which of the ouabain-sensitive Na, K-ATPase alpha subunit isoforms (alpha2 or alpha3) in the brain mediates the pressor responses to increased CSF [Na+]. We hypothesize that the alpha2 isoform mediates the pressor responses to elevated CSF [Na +], such that reduced expression of the alpha2 isoform in mice, via heterozygous gene-targeted knockout, should enhance the pressor response to icv infusion of Na+ or ouabain, compared to wildtype litter mates. These studies suggest a critical role for the alpha2 subunit isoform of the Na, K-ATPase in the pressor response to increased CSF [Na+]. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/27058 |
| Date | January 2005 |
| Creators | Theriault, Steven F |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 125 p. |
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